PROJECT SUMMARY/ABSTRACT Discovering novel natural products that can serve as drugs or drug leads is of critical importance to human health. Our recent work has identified that bacterial symbionts of insects represents a rich, diverse, and largely untapped source of novel compounds. This ICBG focuses on identifying novel natural products from symbiotic bacteria associated with fungus-growing ants and other social insects in Brazil. We will also determine their potential to treat fungal pathogens, Chagas disease, leishmaniasis, and cancer of the blood. In AP3, we will contribute to the overall goals of this ICBG in a number of ways. Working closely with AP1, we will conduct intensive sampling of bacterial symbionts from insects collected from a range of biomes in Brazil. Strains will be catalogue and their 16S rRNA sequenced. Using multilocus sequence typing, we will examine the diversity and host specificity of strains. For 500 strains per year identified to be of highest interest, we will determine both their secondary metabolite potential as well as the ecological context associated with their ability to produce natural products. To do this, we will perform ecological assays between bacterial symbionts and fungal antagonists associate with their insect host, conduct genomic sequencing and analyses, and do in vivo imaging mass spectrometry. Finally, we will provide training to young biologists in fieldwork on bacterial symbionts of insects, tropical microbial ecology, and bioinformatics. Training will include hosting Brazilian students at the University of Wisconsin-Madison, as well as training students from US labs on conducting field research in Brazil.